Browsing by Subject "Epilepsy"
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Item 100% of People Who Confuse Correlation With Causation Eventually Die(Sage, 2024-10-03) Schwalb, Jason M.; Neurological Surgery, School of MedicineItem A Literature Review of Similarities Between and Among Patients With Autism Spectrum Disorder and Epilepsy(Springer Nature, 2023-01-18) Assuah, Freda B.; Emanuel, Bryce; Lacasse, Brianna M.; Beggs, John; Lou, Jennie; Motta, Francis C.; Nemzer, Louis R.; Worth, Robert; Cravens, Gary D.; Mathematical Sciences, School of ScienceAutism spectrum disorder (ASD) has been shown to be associated with various other conditions, and most commonly, ASD has been demonstrated to be linked to epilepsy. ASD and epilepsy have been observed to exhibit high rates of comorbidity, even when compared to the co-occurrence of other disorders with similar pathologies. At present, nearly one-half of the individuals diagnosed with ASD also have been diagnosed with comorbid epilepsy. Research suggests that both conditions likely share similarities in their underlying disease pathophysiology, possibly associated with disturbances in the central nervous system (CNS), and may be linked to an imbalance between excitation and inhibition in the brain. Meanwhile, it remains unclear whether one condition is the consequence of the other, as the pathologies of both disorders are commonly linked to many different underlying signal transduction mechanisms. In this review, we aim to investigate the co-occurrence of ASD and epilepsy, with the intent of gaining insights into the similarities in pathophysiology that both conditions present with. Elucidating the underlying disease pathophysiology as a result of both disorders could lead to a better understanding of the underlying mechanism of disease activity that drives co-occurrence, as well as provide insight into the underlying mechanisms of each condition individually.Item Associations Between Neuroinflammation-Related Conditions and Alzheimer’s Disease: A Study of US Insurance Claims Data(Sage, 2024) Xu, Jing; Chen, Yao; Shi, Yi; Sun, Anna; Yang, Yuedi; Boustani, Malaz; Su, Jing; Zhang, Pengyue; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public HealthBackground: Early detection of Alzheimer's disease (AD) is a key component for the success of the recently approved lecanemab and aducanumab. Patients with neuroinflammation-related conditions are associated with a higher risk for developing AD. Objective: Investigate the incidence of AD among patients with neuroinflammation-related conditions including epilepsy, hemorrhage stroke, multiple sclerosis (MS), and traumatic brain injury (TBI). Methods: We used Optum's de-identified Clinformatics Data Mart Database (CDM). We derived covariate-matched cohorts including patients with neuroinflammation-related conditions and controls without the corresponding condition. The matched cohorts were: 1) patients with epilepsy and controls (N = 67,825 matched pairs); 2) patients with hemorrhage stroke and controls (N = 81,510 matched pairs); 3) patients with MS and controls (N = 9,853 matched pairs); and 4) patients TBI and controls (N = 104,637 matched pairs). We used the Cox model to investigate the associations between neuroinflammation-related conditions and AD. Results: We identified that epilepsy, hemorrhage stroke, and TBI were associated with increased risks of AD in both males and females (hazard ratios [HRs]≥1.74, p < 0.001), as well as in gender- and race-conscious subpopulations (HRs≥1.64, p < 0.001). We identified that MS was associated with increased risks of AD in both males and females (HRs≥1.47, p≤0.004), while gender- and race-conscious subgroup analysis shown mixed associations. Conclusions: Patients with epilepsy, hemorrhage stroke, MS, and/or TBI are associated with a higher risk of developing AD. More attention on cognitive status should be given to older patients with these conditions.Item Biallelic CRELD1 variants cause a multisystem syndrome, including neurodevelopmental phenotypes, cardiac dysrhythmias, and frequent infections(Elsevier, 2024) Jeffries, Lauren; Mis, Emily K.; McWalter, Kirsty; Donkervoort, Sandra; Brodsky, Nina N.; Carpier, Jean-Marie; Ji, Weizhen; Ionita, Cristian; Roy, Bhaskar; Morrow, Jon S.; Darbinyan, Armine; Iyer, Krishna; Aul, Ritu B.; Banka, Siddharth; Chao, Katherine R.; Cobbold, Laura; Cohen, Stacey; Custodio, Helena M.; Drummond-Borg, Margaret; Elmslie, Frances; Finanger, Erika; Hainline, Bryan E.; Helbig, Ingo; Hewson, Stacy; Hu, Ying; Jackson, Adam; Josifova, Dragana; Konstantino, Monica; Leach, Meganne E.; Mak, Bryan; McCormick, David; McGee, Elisabeth; Nelson, Stanley; Nguyen, Joanne; Nugent, Kimberly; Ortega, Lucy; Goodkin, Howard P.; Roeder, Elizabeth; Roy, Sani; Sapp, Katie; Saade, Dimah; Sisodiya, Sanjay M.; Stals, Karen; Towner, Shelley; Wilson, William; Deciphering Developmental Disorders; Genomics England Research Consortium; Undiagnosed Disease Network; Khokha, Mustafa K.; Bönnemann, Carsten G.; Lucas, Carrie L.; Lakhani, Saquib A.; Medical and Molecular Genetics, School of MedicinePurpose: We sought to delineate a multisystem disorder caused by recessive cysteine-rich with epidermal growth factor-like domains 1 (CRELD1) gene variants. Methods: The impact of CRELD1 variants was characterized through an international collaboration utilizing next-generation DNA sequencing, gene knockdown, and protein overexpression in Xenopus tropicalis, and in vitro analysis of patient immune cells. Results: Biallelic variants in CRELD1 were found in 18 participants from 14 families. Affected individuals displayed an array of phenotypes involving developmental delay, early-onset epilepsy, and hypotonia, with about half demonstrating cardiac arrhythmias and some experiencing recurrent infections. Most harbored a frameshift in trans with a missense allele, with 1 recurrent variant, p.(Cys192Tyr), identified in 10 families. X tropicalis tadpoles with creld1 knockdown displayed developmental defects along with increased susceptibility to induced seizures compared with controls. Additionally, human CRELD1 harboring missense variants from affected individuals had reduced protein function, indicated by a diminished ability to induce craniofacial defects when overexpressed in X tropicalis. Finally, baseline analyses of peripheral blood mononuclear cells showed similar proportions of immune cell subtypes in patients compared with healthy donors. Conclusion: This patient cohort, combined with experimental data, provide evidence of a multisystem clinical syndrome mediated by recessive variants in CRELD1.Item Boricua Founder Variant in FRRS1L Causes Epileptic Encephalopathy With Hyperkinetic Movements(Sage, 2021) Abdelmoumen, Imane; Jimenez, Sandra; Valencia, Ignacio; Melvin, Joseph; Legido, Agustin; Diaz-Diaz, Mayela M.; Griffith, Christopher; Massingham, Lauren J.; Yelton, Melissa; Rodríguez-Hernández, Janice; Schnur, Rhonda E.; Walsh, Laurence E.; Cristancho, Ana G.; Bergqvist, Christina A.; McWalter, Kirsty; Mathieson, Iain; Belbin, Gillian M.; Kenny, Eimear E.; Ortiz-Gonzalez, Xilma R.; Schneider, Michael C.; Neurology, School of MedicineObjective: To describe a founder mutation effect and the clinical phenotype of homozygous FRRS1L c.737_739delGAG (p.Gly246del) variant in 15 children of Puerto Rican (Boricua) ancestry presenting with early infantile epileptic encephalopathy (EIEE-37) with prominent movement disorder. Background: EIEE-37 is caused by biallelic loss of function variants in the FRRS1L gene, which is critical for AMPA-receptor function, resulting in intractable epilepsy and dyskinesia. Methods: A retrospective, multicenter chart review of patients sharing the same homozygous FRRS1L (p.Gly246del) pathogenic variant identified by clinical genetic testing. Clinical information was collected regarding neurodevelopmental outcomes, neuroimaging, electrographic features and clinical response to antiseizure medications. Results: Fifteen patients from 12 different families of Puerto Rican ancestry were homozygous for the FRRS1L (p.Gly246del) pathogenic variant, with ages ranging from 1 to 25 years. The onset of seizures was from 6 to 24 months. All had hypotonia, severe global developmental delay, and most had hyperkinetic involuntary movements. Developmental regression during the first year of life was common (86%). Electroencephalogram showed hypsarrhythmia in 66% (10/15), with many older children evolving into Lennox-Gastaut syndrome. Six patients demonstrated progressive volume loss and/or cerebellar atrophy on brain magnetic resonance imaging (MRI). Conclusions: We describe the largest cohort to date of patients with epileptic encephalopathy. We estimate that 0.76% of unaffected individuals of Puerto Rican ancestry carry this pathogenic variant due to a founder effect. Children homozygous for the FRRS1L (p.Gly246del) Boricua variant exhibit a very homogenous phenotype of early developmental regression and epilepsy, starting with infantile spasms and evolving into Lennox-Gastaut syndrome with hyperkinetic movement disorder.Item Central and Peripheral Inflammation: A Common Factor Causing Addictive and Neurological Disorders and Aging-Related Pathologie(MDPI, 2023-06-13) Escobar, Angélica P.; Bonansco, Christian; Cruz, Gonzalo; Dagnino-Subiabre, Alexies; Fuenzalida, Marco; Negrón, Ignacio; Sotomayor-Zárate, Ramón; Martínez-Pinto, Jonathan; Jorquera, Gonzalo; Anatomy, Cell Biology and Physiology, School of MedicineMany diseases and degenerative processes affecting the nervous system and peripheral organs trigger the activation of inflammatory cascades. Inflammation can be triggered by different environmental conditions or risk factors, including drug and food addiction, stress, and aging, among others. Several pieces of evidence show that the modern lifestyle and, more recently, the confinement associated with the COVID-19 pandemic have contributed to increasing the incidence of addictive and neuropsychiatric disorders, plus cardiometabolic diseases. Here, we gather evidence on how some of these risk factors are implicated in activating central and peripheral inflammation contributing to some neuropathologies and behaviors associated with poor health. We discuss the current understanding of the cellular and molecular mechanisms involved in the generation of inflammation and how these processes occur in different cells and tissues to promote ill health and diseases. Concomitantly, we discuss how some pathology-associated and addictive behaviors contribute to worsening these inflammation mechanisms, leading to a vicious cycle that promotes disease progression. Finally, we list some drugs targeting inflammation-related pathways that may have beneficial effects on the pathological processes associated with addictive, mental, and cardiometabolic illnesses.Item Chronic Posttraumatic Epilepsy following Neocortical Undercut Lesion in Mice(Public Library of Science (PLoS), 2016) Ping, Xingjie; Jin, Xiaoming; Department of Anatomy & Cell Biology, IU School of MedicinePosttraumatic epilepsy (PTE) usually develops in a small percentage of patients of traumatic brain injury after a varying latent period. Modeling this chronic neurological condition in rodents is time consuming and inefficient, which constitutes a significant obstacle in studying its mechanism and discovering novel therapeutics for its prevention and treatment. Partially isolated neocortex, or undercut, is known to induce cortical hyperexcitability and epileptiform activity in vitro, and has been used extensively for studying the neurophysiological mechanism of posttraumatic epileptogenesis. However, whether the undercut lesion in rodents causes chronic epileptic seizures has not been systematically characterized. Here we used a miniature telemetry system to continuously monitor electroencephalography (EEG) in adult C57BL mice for up to 3 months after undercut surgery. We found that 50% of animals developed spontaneous seizures between 16-50 days after injury. The mean seizure duration was 8.9±3.6 seconds, and the average seizure frequency was 0.17±0.17 times per day. There was no progression in seizure frequency and duration over the recording period. Video monitoring revealed behavioral arrests and clonic limb movement during seizure attacks. A pentylenetetrazol (PTZ) test further showed increased seizure susceptibility in the undercut mice. We conclude that undercut lesion in mice is a model of chronic PTE that involves spontaneous epileptic seizures.Item Cognitive outcomes after magnetic resonance-guided laser interstitial thermal therapy for mesial temporal lobe epilepsy in adolescent patients(Elsevier, 2024-10-29) Cavaleri, Jonathon M.; Chiang, Jenna A.; Wishart, Danielle M.; Kang, Keiko M.; Ng, Patrick R.; Mendoza, Leanne; Hartline, Kenneth; Van Hirtum-Das, Michele; Agurs, Latanya D.; Kahan, Madeline; Jordan, Brittany; Liu, Charles Y.; Lee, Brian; Chiarelli, Peter A.; Chu, Jason K.; Neurological Surgery, School of MedicineSurgical treatment of medication-resistant mesial temporal lobe epilepsy (MTLE) is associated with cognitive deficits. Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) for MTLE has been shown to result in superior cognitive outcomes in adults when compared to open surgical resection. However, data regarding postoperative cognitive outcomes in adolescent and pediatric patients is limited. We retrospectively reviewed sequential cases of pediatric patients who underwent MRgLITT for MTLE between 2017 and 2023. Patients who had complete preoperative and 12 month postoperative neuropsychological evaluation were analyzed for changes in the neuropsychological domains of cognition, memory, executive functioning, visual scanning, graphomotor speed, and fine motor speed/dexterity. Six adolescent patients who underwent MRgLITT for MTLE (x̄ age = 19.0 years, SD = 1.2) and had complete preoperative and postoperative neuropsychological evaluations were included in the analysis. There were no statistically significant changes across neuropsychological domains when comparing pre- and postoperative cognitive evaluations, including verbal memory scores. Clinically significant changes in phonemic fluency were observed when examining side-specific effects and improved for patients who received right-sided MRgLITT but declined for patients who received left-sided MRgLITT. 50 % of patients achieved Engel I outcome at last follow-up. Our preliminary results suggest minimal adverse neuropsychologic effects following MRgLITT for adolescent MTLE, including preservation of verbal memory. Clinical outcomes were similar with those reported in the literature.Item Comorbidity of attention deficit hyperactivity disorder in a patient with epilepsy: Staring down the challenge of inattention versus nonconvulsive seizures(Elsevier, 2024-02-01) Miller, Derryl J.; Komanapalli, Hannah; Dunn, David W.; Neurology, School of MedicineEpilepsy is a heterogeneous disorder of recurrent seizures which often is comorbid with anxiety, depression, attention deficit hyperactivity disorder (ADHD), intellectual disability (ID), and other psychiatric manifestations. Treating both epilepsy and behavioral symptoms from psychiatric disorders can result in polypharmacy with interactions of medications leading to both worsened efficacy of antiseizure medications due to psychotropic effects and worsening of psychiatric symptoms due to antiseizure medication side effects. We aim to suggest pragmatic strategies for the neurologist in the diagnosis and management of comorbid ADHD in patients with epilepsy based on the International League Against Epilepsy (ILAE) Pediatric Commission guidelines and additional literature review. The screening tool of choice for the symptoms of ADHD is validated in the country of practice and written in the language of the family, though various screening tools and advantages and disadvantages of each will be discussed. Once ADHD is diagnosed, recent safety data suggest that Methylphenidate, Amphetamine, and Atomoxetine are generally safe for patients with epilepsy. We present a case of a child with epilepsy and ADHD and discuss the clinical signs, symptoms, and strategies for treatment as well as when to refer to child psychiatry.Item Connectomic profiling and Vagus nerve stimulation Outcomes Study (CONNECTiVOS): a prospective observational protocol to identify biomarkers of seizure response in children and youth(BMJ, 2022-04-08) Siegel, Lauren; Yan, Han; Warsi, Nebras; Wong, Simeon; Suresh, Hrishikesh; Weil, Alexander G.; Ragheb, John; Wang, Shelly; Rozzelle, Curtis; Albert, Gregory W.; Raskin, Jeffrey; Abel, Taylor; Hauptman, Jason; Schrader, Dewi V.; Bollo, Robert; Smyth, Matthew D.; Lew, Sean M.; Lopresti, Melissa; Kizek, Dominic J.; Weiner, Howard L.; Fallah, Aria; Widjaja, Elysa; Ibrahim, George M.; Neurological Surgery, School of MedicineIntroduction: Vagus nerve stimulation (VNS) is a neuromodulation therapy that can reduce the seizure burden of children with medically intractable epilepsy. Despite the widespread use of VNS to treat epilepsy, there are currently no means to preoperatively identify patients who will benefit from treatment. The objective of the present study is to determine clinical and neural network-based correlates of treatment outcome to better identify candidates for VNS therapy. Methods and analysis: In this multi-institutional North American study, children undergoing VNS and their caregivers will be prospectively recruited. All patients will have documentation of clinical history, physical and neurological examination and video electroencephalography as part of the standard clinical workup for VNS. Neuroimaging data including resting-state functional MRI, diffusion-tensor imaging and magnetoencephalography will be collected before surgery. MR-based measures will also be repeated 12 months after implantation. Outcomes of VNS, including seizure control and health-related quality of life of both patient and primary caregiver, will be prospectively measured up to 2 years postoperatively. All data will be collected electronically using Research Electronic Data Capture. Ethics and dissemination: This study was approved by the Hospital for Sick Children Research Ethics Board (REB number 1000061744). All participants, or substitute decision-makers, will provide informed consent prior to be enrolled in the study. Institutional Research Ethics Board approval will be obtained from each additional participating site prior to inclusion. This study is funded through a Canadian Institutes of Health Research grant (PJT-159561) and an investigator-initiated funding grant from LivaNova USA (Houston, TX; FF01803B IIR).